The research herein proposed has three primary objectives. First, it seeks to determine and describe the molecular mechanisms responsible for Ca2 ions, Mn2 ions, Sr2 ions and Mg2 ions permeability across the inner mitochondrial membrane. The description is to include their charge transfer characteristics, whether or not these mechanisms couple flux of the ions of interest to flux of any other ions on molecules, an information on energy coupling to the transport system. Second, it seeks to isolate these transport mechanisms, if possible. These isolated transport mechanisms along with proteins isolated in other laboratories, whose isolation is described in the literature, are to be tested in cytochrome oxidase vesicles in an effort to reconstitute part or all of the mitochondrial divalent ion transport system. Finally, this research project seeks to cast light on the physiological significance of mitochondrial Ca2 ions transport by determining which substrates or products of cytosolic or nuclear processes sensitive to Ca2 ions inhibit or activate parts of the Ca2 ions transport mechanism.